Primary hyperparathyroidism
Classification and external resources
Thyroid and parathyroid.
ICD-10	E21.0
ICD-9	252.01
DiseasesDB	6283
eMedicine	radio/355
MeSH	D049950

Primary hyperparathyroidism causes hypercalcemia (elevated blood calcium levels) through the excessive secretion of parathyroid hormone (PTH), usually by an adenoma (benign tumors) of the parathyroid glands. Its incidence is approximately 42 per 100,000 people. It is almost exactly three times as common in women as men.

Contents 1 Signs and Symptoms 2 Diagnosis 2.1 Parathyroid hormone activity 3 Causes 4 Complications 5 Treatment 5.1 Medications 5.2 Surgery 5.3 Future therapies 6 See also 7 References

[edit] Signs and Symptoms

The signs and symptoms of primary hyperparathyroidism are those of hypercalcemia. They are classically summarized by the mnemonic "stones, bones, abdominal groans and psychic moans".

• "Stones" refers to kidney stones, nephrocalcinosis, and diabetes insipidus (polyuria and polydipsia). These can ultimately lead to renal failure.
• "Bones" refers to bone-related complications. The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.
• "Abdominal groans" refers to gastrointestinal symptoms of constipation, indigestion, nausea and vomiting. Hypercalcemia can lead to peptic ulcers and acute pancreatitis.
• "Psychic moans" refers to effects on the central nervous system. Symptoms include lethargy, fatigue, depression, memory loss, psychosis, ataxia, delirium, and coma.
• Left ventricular hypertrophy.^[1]
• Increased all cause mortality^[2]

The German description of the same symptoms is "Stein-, Bein- und Magenpein", literally "stone, leg, and stomach-pain".

Other signs include proximal muscle weakness, itching, and band keratopathy of the eyes.

[edit] Diagnosis

The diagnosis of primary hyperparathyroidism is made by blood tests. Serum calcium levels are elevated.

The serum chloride phosphate ratio is 33 or more in most patients with primary hyperparathyroidism.^[3][4][5] However, thiazide medications have been reported to causes ratios above 33.^[6]

Urinary cAMP is occasionally measured; this is generally elevated..

[edit] Parathyroid hormone activity

Intact PTH levels are also elevated.

[edit] Causes

The most common cause of primary hyperparathyroidism is a sporadic, single parathyroid adenoma^[7] resulting from a clonal mutation (~97%). Less common are parathyroid hyperplasia^[7] (~2.5%), parathyroid carcinoma (malignant tumor), and adenomas in more than one gland (together ~0.5%).

Primary hyperparathyroidism is also a feature of several familial endocrine disorders: Multiple endocrine neoplasia type 1 and type 2A (MEN type 1 and MEN type 2A), and familial hyperparathyroidism.

Genetic associations include:

OMIM	Name	Gene
145000	HRPT1	MEN1, HRPT2
145001	HRPT2	HRPT2
610071	HRPT3	unknown at 2p13.3-14[8]

In all cases, the disease is idiopathic, but is thought to involve inactivation of tumor suppressor genes (Menin gene in MEN1), or involve gain of function mutations (RET proto-oncogene MEN 2a).

[edit] Complications

The classic bone disease in hyperparathyroidism is osteitis fibrosa cystica, which results in pain and sometimes pathological fractures. Other bone diseases associated with hyperparathyroidism are osteoporosis, osteomalacia, and arthritis.

[edit] Treatment

Treatment is usually surgical removal of the gland(s) containing adenomas.

[edit] Medications

Medications include estrogen replacement therapy in postmenopausal women and bisphosphonates. Bisphosphonates may improve bone turnover.^[9] Newer medications termed "calcimimetics" used in secondary hyperparathyroidism are now being used in Primary hyperparathyroidism. Calcimimetics reduce the amount of parathyroid hormone released by the parathyroid glands. They are recommended in patients in whom surgery is inappropriate.

[edit] Surgery

The symptoms of the disease, listed above, are indications for surgery. Surgery reduces all cause mortality as well as resolving symptoms. However, cardiovascular mortality is not significantly reduced^[10]

A consensus statement in 2002 recommended the following indications for surgery in asymptomatic hyperparathyroidism^[11]:

• Serum calcium (above upper limit of normal): 1.0 mg/dl
• 24-h urinary calcium >400 mg
• Creatinine clearance reduced by 30% compared with age-matched subjects.
• Bone mineral density t-score <−2.5 at any site
• Age <50

More recently, three randomized controlled trials have studied the role of surgery in patients with asymptomatic hyperparathyroidism. The largest study reported that surgery showed increase in bone mass, but no improvement in quality of life after one to two years among patients with^[12]:

• Untreated, asymptomatic primary hyperparathyroidism
• Serum calcium between 2.60–2.85 mmol/liter (10.4–11.4 mg/dl)
• Age between 50 and 80 yr
• No medications interfering with Ca metabolism
• No hyperparathyroid bone disease
• No previous operation in the neck
• Creatinine level < 130 µmol/liter (<1.47 mg/dl)

Two other trials reported improvements in bone density and some improvement in quality of life with surgery.^[13][14]

[edit] Future therapies

Future developments such as calcimemetic agents (e.g. cinacalcet) which activate the parathyroid calcium-sensing receptor may offer a good alternative to surgery.

[edit] See also

• Secondary hyperparathyroidism
• Tertiary hyperparathyroidism

[edit] References

v • d • e Endocrine pathology: endocrine diseases (E00-35, 240-259) Pancreas/ glucose metabolism Hypofunction Diabetes mellitus types: (type 1, type 2, MODY 1 2 3 4 5 6) · complications (coma, angiopathy, ketoacidosis, nephropathy, neuropathy, retinopathy, cardiomyopathy) insulin receptor (Rabson-Mendenhall syndrome) · Insulin resistance Hyperfunction Hypoglycemia · beta cell (Hyperinsulinism) · G cell (Zollinger-Ellison syndrome) Hypothalamic/ pituitary axes Hypothalamus gonadotropin (Kallmann syndrome, Adiposogenital dystrophy) · CRH (Tertiary adrenal insufficiency) · vasopressin (Neurogenic diabetes insipidus) · general (Hypothalamic hamartoma) Pituitary Hyperpituitarism anterior (Acromegaly, Hyperprolactinaemia, Pituitary ACTH hypersecretion) · posterior (SIADH) · general (Nelson's syndrome) Hypopituitarism anterior (Kallmann syndrome, Growth hormone deficiency, ACTH deficiency/Secondary adrenal insufficiency) · posterior (Neurogenic diabetes insipidus) · general (Empty sella syndrome, Pituitary apoplexy, Sheehan's syndrome, Lymphocytic hypophysitis) Thyroid Hypothyroidism Iodine deficiency · Cretinism (Congenital hypothyroidism) · Myxedema · Euthyroid sick syndrome Hyperthyroidism Hyperthyroxinemia (Thyroid hormone resistance, Familial dysalbuminemic hyperthyroxinemia) · Hashitoxicosis · Thyrotoxicosis factitia · Graves' disease Thyroiditis Acute infectious · Subacute (De Quervain's, Subacute lymphocytic) · Autoimmune/chronic (Hashimoto's, Postpartum, Riedel's) Goitre Endemic goitre · Toxic nodular goitre · Toxic multinodular goitre Thyroid nodule Parathyroid Hypoparathyroidism Pseudohypoparathyroidism Hyperparathyroidism Primary · Secondary · Tertiary · Osteitis fibrosa cystica Adrenal Hyperfunction aldosterone: Hyperaldosteronism/Primary aldosteronism (Conn syndrome, Bartter syndrome, Glucocorticoid remediable aldosteronism) · AME · Liddle's syndrome · 17α CAH cortisol: Cushing's syndrome (Pseudo-Cushing's syndrome) sex hormones: 21α CAH · 11β CAH Hypofunction/ Adrenal insufficiency (Addison's, WF) aldosterone: Hypoaldosteronism (21α CAH, 11β CAH) cortisol: CAH (Lipoid, 3β, 11β, 17α, 21α) sex hormones: 17α CAH Gonads ovarian: Polycystic ovary syndrome · Premature ovarian failure testicular: enzymatic (5-alpha-reductase deficiency, 17-beta-hydroxysteroid dehydrogenase deficiency) · Androgen receptor (Androgen insensitivity syndrome) general: Hypogonadism (Delayed puberty) · Hypergonadism (Precocious puberty) Height Gigantism · Dwarfism/Short stature (Laron syndrome, Psychogenic dwarfism) Multiple Autoimmune polyendocrine syndrome (APS1, APS2) · Carcinoid syndrome · Multiple endocrine neoplasia (1, 2A, 2B) · Progeria · Woodhouse-Sakati syndrome endocrine navs: anat/physio/dev/hormones, noncongen/congen/neoplasia, symptoms+signs/eponymous, proc